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Study · In vitro (cells) · mouse · 2013

3 results

Agonist-biased trafficking of somatostatin receptor 2A in enteric neurons.

Zhao P, Canals M, Murphy JE, Klingler D, Eriksson EM, Pelayo JC, Hardt M, Bunnett NW, Poole DP

The Journal of biological chemistry2 Aug 2013Cited by 33 (Europe PMC)

PMID23913690 (opens in a new tab)PMCIDPMC3764777 (opens in a new tab)DOI10.1074/jbc.m113.496414 (opens in a new tab)PepBankPUB-23913690
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Summary

Somatostatin (SST) 14 and SST 28 activate somatostatin 2A receptors (SSTR2A) on enteric neurons to control gut functions. SST analogs are treatments of neuroendocrine and bleeding disorders, cancer, and diarrhea, with gastrointestinal side effects of constipation, abdominal pain, and nausea. How endogenous agonists and drugs differentially regulate neuronal SSTR2A is unexplored. We evaluated SSTR2A trafficking in murine myenteric neurons and neuroendocrine AtT-20 cells by microscopy and determined whether agonist degradation by endosomal endothelin-converting enzyme 1 (ECE-1) controls SSTR2A trafficking and association with β-arrestins, key regulators of receptors. SST-14, SST-28, and peptide analogs (octreotide, lanreotide, and vapreotide) stimulated clathrin- and dynamin-mediated internalization of SSTR2A, which colocalized with ECE-1 in endosomes and the Golgi. After incubation with SST-14, SSTR2A recycled to the plasma membrane, which required active ECE-1 and an intact Golgi. SSTR2A activated by SST-28, octreotide, lanreotide, or vapreotide was retained within the Golgi and did not recycle. Although ECE-1 rapidly degraded SST-14, SST-28 was resistant to degradation, and ECE-1 did not degrade SST analogs. SST-14 and SST-28 induced transient interactions between SSTR2A and β-arrestins that were stabilized by an ECE-1 inhibitor. Octreotide induced sustained SSTR2A/β-arrestin interactions that were not regulated by ECE-1. Thus, when activated by SST-14, SSTR2A internalizes and recycles via the Golgi, which requires ECE-1 degradation of SST-14 and receptor dissociation from β-arrestins. After activation by ECE-1-resistant SST-28 and analogs, SSTR2A remains in endosomes because of sustained β-arrestin interactions. Therapeutic SST analogs are ECE-1-resistant and retain SSTR2A in endosomes, which may explain their long-lasting actions.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Mechanism

    In murine neurons and AtT-20 cell experiments, lanreotide stimulated clathrin- and dynamin-mediated SSTR2A internalization with ECE-1 colocalization in endosomes and Golgi.

    In plain wordsIn lab tests, lanreotide stimulated receptor internalization, with receptors and ECE-1 together in endosomes and the Golgi.

    Peptide
    Lanreotide
    Outcome
    IncreaseSSTR2A internalization
    Study

    mousen: not reported in source

    Murine myenteric neurons and neuroendocrine AtT-20 cells
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    SST-14, SST-28, and peptide analogs (octreotide, lanreotide, and vapreotide) stimulated clathrin- and dynamin-mediated internalization of SSTR2A, which colocalized with ECE-1 in endosomes and the Golgi.
    1 context sentence
    Summary · context
    We evaluated SSTR2A trafficking in murine myenteric neurons and neuroendocrine AtT-20 cells by microscopy and determined whether agonist degradation by endosomal endothelin-converting enzyme 1 (ECE-1) controls SSTR2A trafficking and association with β-arrestins, key regulators of receptors.
  2. 02LabIn vitro (cells)Mechanism

    In murine neurons and AtT-20 cell experiments, lanreotide-activated SSTR2A remained in the Golgi and did not recycle.

    In plain wordsIn lab tests, receptors activated by lanreotide remained in the Golgi and did not recycle.

    Peptide
    Lanreotide
    Outcome
    Not applicableSSTR2A Golgi retention and recycling
    Study

    mousen: not reported in source

    Murine myenteric neurons and neuroendocrine AtT-20 cells
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    SSTR2A activated by SST-28, octreotide, lanreotide, or vapreotide was retained within the Golgi and did not recycle.
    1 context sentence
    Summary · context
    We evaluated SSTR2A trafficking in murine myenteric neurons and neuroendocrine AtT-20 cells by microscopy and determined whether agonist degradation by endosomal endothelin-converting enzyme 1 (ECE-1) controls SSTR2A trafficking and association with β-arrestins, key regulators of receptors.
  3. 03LabIn vitro (cell-free)Mechanism

    In laboratory experiments, ECE-1 did not degrade somatostatin analogs, including lanreotide.

    In plain wordsIn lab tests, ECE-1 did not degrade somatostatin analogs, including lanreotide.

    Peptide
    Lanreotide
    Outcome
    No significant changeResistance to ECE-1 degradation
    Study

    n: not reported in source

    ECE-1 degradation experiments
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Although ECE-1 rapidly degraded SST-14, SST-28 was resistant to degradation, and ECE-1 did not degrade SST analogs.
    1 context sentence
    Summary · context
    SST-14, SST-28, and peptide analogs (octreotide, lanreotide, and vapreotide) stimulated clathrin- and dynamin-mediated internalization of SSTR2A, which colocalized with ECE-1 in endosomes and the Golgi.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:36 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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